SDS of cas: 84547-64-8. The fused heterocycle is formed by combining a benzene ring with a single heterocycle, or two or more single heterocycles. Compound: 3-(Chloromethyl)-1-methyl-1H-pyrazole, is researched, Molecular C5H7ClN2, CAS is 84547-64-8, about Discovery of the First α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Antagonist Dependent upon Transmembrane AMPA Receptor Regulatory Protein (TARP) γ-8. Author is Gardinier, Kevin M.; Gernert, Douglas L.; Porter, Warren J.; Reel, Jon K.; Ornstein, Paul L.; Spinazze, Patrick; Stevens, F. Craig; Hahn, Patric; Hollinshead, Sean P.; Mayhugh, Daniel; Schkeryantz, Jeff; Khilevich, Albert; De Frutos, Oscar; Gleason, Scott D.; Kato, Akihiko S.; Luffer-Atlas, Debra; Desai, Prashant V.; Swanson, Steven; Burris, Kevin D.; Ding, Chunjin; Heinz, Beverly A.; Need, Anne B.; Barth, Vanessa N.; Stephenson, Gregory A.; Diseroad, Benjamin A.; Woods, Tim A.; Yu, Hong; Bredt, David; Witkin, Jeffrey M..
Transmembrane AMPA receptor regulatory proteins (TARPs) are a family of scaffolding proteins that regulate AMPA receptor trafficking and function. TARP γ-8 is one member of this family and is highly expressed within the hippocampus relative to the cerebellum. A selective TARP γ-8-dependent AMPA receptor antagonist (TDAA) is an innovative approach to modulate AMPA receptors in specific brain regions to potentially increase the therapeutic index relative to known non-TARP-dependent AMPA antagonists. We describe here, for the first time, the discovery of a noncompetitive AMPA receptor antagonist that is dependent on the presence of TARP γ-8. Three major iteration cycles were employed to improve upon potency, CYP1A2-dependent challenges, and in vivo clearance. An optimized mol., compound (-)-25 (LY3130481), was fully protective against pentylenetetrazole-induced convulsions in rats without the motor impairment associated with non-TARP-dependent AMPA receptor antagonists. Compound (-)-25 could be utilized to provide proof of concept for antiepileptic efficacy with reduced motor side effects in patients.
Different reactions of this compound(3-(Chloromethyl)-1-methyl-1H-pyrazole)SDS of cas: 84547-64-8 require different conditions, so the reaction conditions are very important.
Reference:
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